This project deals with the metabolism of a toxic element cadmium in an animal model. The absorption, tissue distribution and excretion of an orally administered isotope of cadmium will be followed in rats. The biological half-life of cadmium in the rat in general, and in the critical organs liver and kidney in particular, will be determined. Retention of cadmium in the critical organs is brought about by metallothionein. The mechanism by which cadmium stimulates protein synthesis in these organs will be investigated. Cadmium is bound to metallothionein not only in liver and kidney, but also in other tissues like pancrease, spleen and placenta. The proteins from these organs will be isolated and purified and their properties will be compared with the hepatic protein. A radioimmunoassay procedure will be developed to measure metallothionein in tissues and biological fluids. It is postulated that intestinal absorption of cadmium and the passage of the element from the mother to fetus and newborn may be restricted by the presence of metallothionein and other metal-binding proteins in intestinal mucosa, placenta and mammary gland. The validity of this concept will be tested in animals experimentally exposed to cadmium. Involvement of cadmium in renal tubular dysfunction and hypertension has been suggested. The role of metallothionein in etiology of these diseases will be evaluated.